Affinage

FGF18

Fibroblast growth factor 18 · UniProt O76093

Length
207 aa
Mass
24.0 kDa
Annotated
2026-06-09
100 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FGF18 is a secreted, glycosylated signaling protein that acts as a paracrine and autocrine growth factor coordinating skeletal, epithelial, neuromuscular, and tissue-repair programs (PMID:9660775, PMID:9742123). It binds selectively to FGFR3c and FGFR2c, but not FGFR1c, and engages these receptors in a heparan sulfate–dependent manner to activate ERK, p38 MAPK, and AKT/GSK3β/β-catenin signaling (PMID:9742123, PMID:12399108, PMID:15781473). In the skeleton FGF18 is a positive regulator of osteogenesis and a context-dependent regulator of chondrogenesis: knockout mice show delayed suture closure and altered chondrocyte proliferation, and FGF18 drives osteoblast/chondrocyte proliferation through ERK (and p38 in chondrocytes), promotes osteoclast formation via RANKL/COX-2, suppresses noggin to enhance BMP-dependent chondrogenesis, and is required for VEGF-driven growth plate vascularization (PMID:11741978, PMID:11937494, PMID:15252029, PMID:17014841); it acts redundantly with FGF9 upstream of IHH, PTHrP, and RUNX2 (PMID:26794256). Beyond bone, FGF18 maintains hair follicle stem cell quiescence and the resting (telogen) phase of the hair cycle (PMID:22297635, PMID:23946441), is required for acetylcholine receptor clustering and neuromuscular junction formation via FGFR/MEK1 signaling (PMID:29323161), promotes lung branching morphogenesis and alveologenesis (PMID:15336546, PMID:36791060), and regulates limb myogenesis through ERK-dependent induction of Myf5/MyoD (PMID:25446536). FGF18 transcription is a convergence point for multiple regulatory inputs, most prominently canonical Wnt signaling acting through a composite β-catenin/TCF-Runx2 element in its promoter, as well as calcineurin/NFAT4, Glis3, Foxp1, Foxf1/2, and Creb5/TGF-β (PMID:14559787, PMID:15252029, PMID:17158875, PMID:17488195, PMID:23946441, PMID:26745863, PMID:36542062). Extracellular FGF18 activity is tuned by direct binding to perlecan domain III, which antagonizes its mitogenic effect, and by the co-receptor Cfr/Glg1, whose interaction with FGF18 is blocked by Dlk (PMID:17971291, PMID:20023171). In cancers FGF18 promotes EMT, migration, and angiogenesis through AKT/GSK3β/β-catenin and FGFR2-driven c-Jun–YAP1 signaling (PMID:30196303, PMID:29242604, PMID:32934314). Following receptor activation, FGF18 (sprifermin) undergoes clathrin- and dynamin-independent endocytosis and is co-degraded with FGFR3, producing transient receptor desensitization (PMID:32798495).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1998 Medium

    Established FGF18 as a bona fide secreted signaling molecule with mitogenic/differentiation-inducing activity, defining the basic biochemical identity that all later mechanism rests on.

    Evidence Recombinant rat/murine FGF18 in neurite outgrowth and fibroblast proliferation assays plus in vivo overexpression

    PMID:9660775 PMID:9742123

    Open questions at the time
    • Receptor specificity not yet defined
    • In vivo target tissues identified phenomenologically without pathway dissection
  2. 2002 High

    Defined FGF18 receptor selectivity and the core signaling outputs, answering which FGFRs transduce its signal and through which kinases.

    Evidence BIAcore binding to FGFR3c/FGFR2c vs FGFR1c, and ERK/p38 phosphorylation dissection in osteoblasts and chondrocytes with kinase inhibitors

    PMID:11741978 PMID:12399108

    Open questions at the time
    • Cell-type-specific receptor usage not resolved
    • Heparan sulfate dependence quantified only indirectly
  3. 2002 High

    Demonstrated the in vivo skeletal role, showing FGF18 is a positive osteogenic and negative chondrogenic regulator and resolving its physiological function in bone.

    Evidence Fgf18−/− mice with histology and proliferation assays across calvaria and growth plate

    PMID:11937494

    Open questions at the time
    • Receptor mediating each effect not genetically assigned
    • Opposite effects on osteoblasts vs chondrocytes mechanistically unexplained
  4. 2003 High

    Placed FGF18 transcription downstream of canonical Wnt/β-catenin signaling and linked it to autocrine tumor growth, connecting a developmental pathway to cancer.

    Evidence Promoter reporter, EMSA for TCF4 sites, and FGF18 siRNA in colon cancer cells

    PMID:14559787

    Open questions at the time
    • Composite promoter architecture not yet defined
    • In vivo relevance of Wnt control not tested here
  5. 2005 High

    Assigned FGFR3 as the functional receptor for FGF18 in chondrogenesis and showed FGF18 controls vascularization, integrating cartilage and bone development.

    Evidence FGFR3−/− limb bud mesenchyme cultures and Fgf18−/− analysis with VEGF in situ and explant rescue

    PMID:15781473 PMID:17014841

    Open questions at the time
    • Contribution of FGFR2c not separated
    • Downstream transcriptional effectors of VEGF induction unknown
  6. 2006 High

    Resolved the composite transcriptional mechanism by showing Runx2 forms a complex with Lef1/TCF4 on the FGF18 promoter, and that calcineurin/NFAT4 and Glis3 also drive its expression.

    Evidence Reporter, EMSA, Co-IP of Runx2-Lef1/TCF4, in vivo β-catenin conditional KO; NFAT4 and Glis3 gain/loss-of-function

    PMID:15252029 PMID:17158875 PMID:17488195

    Open questions at the time
    • Combinatorial logic of multiple inputs not integrated
    • Cell-type specificity of each transcription factor not mapped
  7. 2010 High

    Identified extracellular modulators of FGF18 activity, showing perlecan domain III directly binds and antagonizes it and that the co-receptor Cfr/Glg1 promotes signaling while Dlk competes Cfr away.

    Evidence Kd binding/domain mapping with recombinant perlecan; Cfr KO epistasis, Co-IP (Cfr-FGF18, Cfr-Dlk), Ba/F3 proliferation

    PMID:17971291 PMID:20023171

    Open questions at the time
    • Structural basis of perlecan and Cfr binding unknown
    • How Cfr couples to FGFR3 mechanistically unresolved
  8. 2013 High

    Established FGF18 as the effector maintaining hair follicle stem cell quiescence and resolved its upstream control by Foxp1, ordering the niche signaling pathway.

    Evidence Conditional Fgf18 and Foxp1 KO with FGF18 rescue of Foxp1-null phenotype and in vivo protein delivery

    PMID:22297635 PMID:23946441

    Open questions at the time
    • Receptor mediating quiescence signal not identified
    • Downstream effectors of FGF18 in stem cells unknown
  9. 2016 High

    Extended FGF18 into craniofacial and limb developmental circuits, defining Shh-Foxf-Fgf18 feedback and FGF9/18 redundancy upstream of IHH/PTHrP/RUNX2.

    Evidence Conditional Foxf1/2 KO with explant FGF18 inhibition of Shh; combined Fgf9/Fgf18 allele series

    PMID:26745863 PMID:26794256

    Open questions at the time
    • Receptor specificity in palate not assigned
    • Quantitative contribution of FGF9 vs FGF18 at each site unresolved
  10. 2018 High

    Revealed a neuromuscular role, showing motor-neuron FGF18 is required for AChR clustering and NMJ maturation through FGFR/MEK1, broadening FGF18 function beyond mesenchyme.

    Evidence Fgf18−/− mice with electrophysiology and ultrastructure plus C2C12 clustering assay with FGFR/MEK1 inhibitors

    PMID:29323161

    Open questions at the time
    • Specific FGFR isoform at the NMJ not identified
    • Link to AChR clustering machinery (MuSK/agrin) not defined
  11. 2020 Medium

    Defined cancer-associated signaling outputs, showing FGF18-FGFR2 drives a c-Jun–YAP1 axis and that FGF18/sprifermin desensitizes cells via endocytic co-degradation with FGFR3.

    Evidence FGFR2 siRNA/AZD4547 with YAP1 readouts; endocytosis tracing with clathrin/dynamin inhibitors and FGFR3 degradation assays

    PMID:32798495 PMID:32934314

    Open questions at the time
    • Endocytic receptor for ligand uptake unidentified
    • Whether FGFR2-YAP1 axis operates outside gastric cancer untested
  12. 2023 High

    Established FGF18 as a paracrine regulator of liver injury and fibrosis, acting through USP16/KEAP1/Nrf2 protection and an OPN-mediated feedforward fibrotic loop.

    Evidence HSC-specific FGF18 deletion, Co-IP and ubiquitination assays, ChIP, and activated vs quiescent HSC cultures

    PMID:37777507 PMID:40678531

    Open questions at the time
    • Receptor mediating hepatic FGF18 effects not defined
    • Whether protective and profibrotic roles depend on injury context unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FGF18's distinct downstream programs (ERK proliferation vs AKT/β-catenin EMT vs YAP1 vs Nrf2) are selected in a given cell, and which FGFR isoform mediates each non-skeletal function, remains unresolved.
  • No unified model linking receptor choice to pathway output
  • Structural mechanism of receptor/co-receptor selectivity uncharacterized
  • Endocytic uptake receptor for sprifermin unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0060089 molecular transducer activity 3
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4
Partners
DLK1FGFR2FGFR3GLG1HSPG2

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 FGF-18 is a secreted, glycosylated protein (207 amino acids) with a typical N-terminal signal sequence. Recombinant rat FGF-18 expressed in insect cells induced neurite outgrowth in PC12 cells, establishing its activity as a signaling molecule. Recombinant protein expression (baculovirus/insect cells), PC12 neurite outgrowth assay The Journal of biological chemistry Medium 9660775
1998 Recombinant murine FGF-18 stimulated proliferation of NIH 3T3 fibroblasts in vitro in a heparan sulfate-dependent manner, and in vivo administration induced proliferation in liver and small intestine, identifying these as primary target tissues. In vitro proliferation assay (NIH 3T3), in vivo injection into normal mice and liver-specific transgenic overexpression Molecular and cellular biology Medium 9742123
2001 FGF-18 stimulates proliferation of osteoblasts and chondrocytes via ERK phosphorylation, and additionally via p38 MAPK in chondrocytes. FGF-18 also induces osteoclast formation through RANKL and COX-2 upregulation and stimulates osteoclast resorption activity. Primary cell cultures (osteoblasts, chondrocytes, osteoclast coculture), ERK/p38 phosphorylation assays, specific kinase inhibitors, dentine resorption pit assay The Journal of biological chemistry High 11741978
2002 Fgf18 knockout mice show delayed suture closure, decreased calvarial osteogenic mesenchymal cell proliferation, delayed terminal osteoblast differentiation, and increased chondrocyte proliferation and differentiation, establishing FGF18 as a positive regulator of osteogenesis and negative regulator of chondrogenesis in vivo. Gene targeting (Fgf18−/− mice), histological analysis, cell proliferation assays Genes & development High 11937494
2002 FGF-18 binds FGF receptors 3c and 2c but not FGFR-1c (as measured by BIAcore surface plasmon resonance), and has mitogenic activity for astrocytes and microglia but not neurons, identifying it as a neuron-derived glial cell growth factor. BIAcore surface plasmon resonance binding assay, primary cell culture mitogenic assays (astrocytes, microglia, cortical neurons) Brain research. Molecular brain research Medium 12399108
2003 FGF18 is a direct transcriptional target of the β-catenin/TCF4 (Wnt) pathway. Reporter gene and EMSA assays demonstrated that the FGF18 promoter contains functional TCF4-binding motifs. Exogenous FGF18 promoted NIH 3T3 cell growth in an autocrine manner; siRNA knockdown of FGF18 suppressed colon cancer cell growth. Luciferase reporter assay, electromobility shift assay (EMSA), siRNA knockdown, cell proliferation assay Cancer research High 14559787
2004 Calcium-dependent signals through calcineurin phosphatase and the transcription factor NFAT4 induce FGF18 expression. FGF18 (or constitutively active FGFR) suppresses noggin gene induction, thereby enhancing BMP-dependent chondrocyte differentiation and chondrogenesis. Expression of activated calcineurin/NFAT4 constructs, FGF18 treatment of chondrocytes, noggin reporter assays, chondrogenesis assays The Journal of biological chemistry Medium 15252029
2004 Fgf18-deficient mouse lungs at E18.5 show reduced alveolar space and thicker interstitial mesenchymal compartments with transiently reduced cell proliferation around E17.5, establishing FGF18 as required for embryonic lung alveolar development. Fgf18−/− knockout mice, histological analysis, cell proliferation assays Biochemical and biophysical research communications Medium 15336546
2005 FGF18 signals through FGFR3 to promote chondrogenesis in limb bud mesenchymal cells: FGFR3−/− cultures show impaired cartilage nodule formation, impaired mitogenic response to FGF18, decreased type II collagen and proteoglycan production, altered integrin expression, and altered FGFR1/2 expression in response to FGF18. FGFR3+/+ vs FGFR3−/− limb bud mesenchymal cell cultures, confocal laser-scanning microscopy, FGF18 stimulation assays The Journal of biological chemistry High 15781473
2005 FGF18 mRNA is highly expressed in hair follicles (anagen inner root sheath and telogen bulge). Subcutaneous administration of FGF18 to mice in telogen induced anagen hair growth, and FGF18 stimulated DNA synthesis in dermal fibroblasts, dermal papilla cells, keratinocytes, and endothelial cells in culture. In situ hybridization, subcutaneous protein injection in vivo, DNA synthesis assay (BrdU/thymidine incorporation) in cultured cells The Journal of investigative dermatology Medium 15854025
2006 FGF18 is required for VEGF expression in hypertrophic chondrocytes and perichondrium, and is sufficient to induce VEGF expression in skeletal explants, coordinating growth plate vascularization with osteoblast/osteoclast recruitment. Loss of FGF18 delays chondrocyte hypertrophy, early chondroprogenitor proliferation, skeletal vascularization, and osteoblast/osteoclast recruitment. Fgf18−/− knockout analysis, Vegf expression analysis by in situ hybridization, FGF18 skeletal explant stimulation assay Developmental biology High 17014841
2006 FGF18 is a direct target of canonical Wnt signaling through a single TCF/Lef-binding site in its promoter. Runx2 and TCF/Lef cooperate to induce FGF18 expression: Runx2 forms a complex with Lef1 or TCF4 that binds the composite binding site in the fgf18 promoter. Targeted disruption of β-catenin blocks fgf18 expression in vivo. Promoter reporter assay, EMSA, RNAi knockdown of Runx2, Runx2 forced expression, co-immunoprecipitation of Runx2-Lef1/TCF4 complex, in vivo β-catenin conditional knockout The Journal of biological chemistry High 17158875
2007 The core protein of growth plate perlecan (domain III, cysteine-rich regions) binds FGF-18 directly with Kd ~27.8–145 nM independent of its heparan sulfate or chondroitin sulfate chains (binding not reduced by glycosaminoglycanase digestion but reduced by reduction/alkylation). Perlecan binding reverses the mitogenic effect of FGF-18 on growth plate chondrocytes by 37–74%. Cationic filtration binding assay, immunoprecipitation, recombinant perlecan domain expression in COS-7 cells, chondroitinase/heparitinase digestion, 3H-thymidine incorporation assay Archives of biochemistry and biophysics High 17971291
2007 The zinc finger protein Glis3 directly binds a Glis3-binding site in the FGF18 promoter and induces FGF18 expression, promoting osteoblast differentiation. RNAi knockdown of Glis3 decreased FGF18 expression, while Glis3 overexpression induced it. Promoter reporter assay, EMSA, microarray, RNAi, gain-of-function in C3H10T1/2 cells Journal of bone and mineral research Medium 17488195
2010 Cysteine-rich FGF receptor (Cfr/Glg1) physically interacts with FGF18 and genetically cooperates with FGF18 signaling. Cfr-deficient mice exhibit phenotypes similar to Fgf18-deficient mice; Cfr facilitates FGF18-dependent proliferation of Ba/F3 cells expressing FGFR3c. Delta-like protein (Dlk) binds Cfr and interrupts Cfr-FGF18 interaction, acting antagonistically. Cfr knockout mice, genetic epistasis (Cfr/Fgf18 compound mutants), co-immunoprecipitation (Cfr-FGF18, Cfr-Dlk), Ba/F3 cell proliferation assay Development (Cambridge, England) High 20023171
2012 Epithelial FGF18 expression in the hair stem cell niche during telogen maintains the resting phase of the hair cycle. Conditional knockout of Fgf18 in keratin 5-positive epithelial cells causes dramatically shortened telogen and rapid hair cycling; local FGF18 delivery suppresses hair follicle growth during anagen. Conditional (K5-Cre) Fgf18 knockout mice, in vivo FGF18 protein delivery, hair cycle analysis The Journal of investigative dermatology High 22297635
2013 Foxp1 maintains hair follicle stem cell quiescence by directly regulating FGF18 expression. Loss of Foxp1 in skin epithelial cells leads to shortened telogen and precocious stem cell activation; exogenous FGF18 rescues premature stem cell activation in Foxp1-null mice, placing FGF18 as a key downstream target of Foxp1. Conditional Foxp1 knockout, Foxp1 overexpression, exogenous FGF18 rescue experiment in Foxp1-null mice, hair cycle analysis Development (Cambridge, England) High 23946441
2013 FGF18 and FGF8 signal through divergent intracellular pathways in bovine granulosa cells: FGF8 increases ERK1/2 phosphorylation and induces SPRY1/2/4, NR4A1/3, and FOS expression, whereas FGF18 does not activate ERK1/2 or induce these genes. FGF18 activates EGR1, FOSL1, BAMBI, PLK2 but not FOS or XIRP1. Primary bovine granulosa cell culture, ERK1/2 phosphorylation assay, microarray gene expression analysis, qPCR validation Molecular and cellular endocrinology Medium 23707615
2015 PHLPP1 phosphatase deficiency leads to increased FGF18 expression via a FoxO1-dependent mechanism, and elevated FGF18 drives increased MEK/ERK activity and chondrocyte metabolic activity. Chemical inhibition of FGFR signaling abrogated the elevated ERK1/2 phosphorylation in Phlpp1-null cultures, placing FGF18/FGFR downstream of PHLPP1/FoxO1. Phlpp1−/− knockout mice and chondrocyte cultures, FGFR chemical inhibitor epistasis, phosphorylation assays (Akt2, PKC, p70S6K, ERK1/2), metabolic activity assays The Journal of biological chemistry Medium 25953896
2016 A Shh-Foxf-Fgf18-Shh circuit operates in palate development: Foxf1 and Foxf2 repress Fgf18 expression in palatal mesenchyme downstream of Shh signaling; elevated FGF18 (in Foxf mutants) inhibits Shh expression in the palatal epithelium. Exogenous FGF18 protein added to cultured palatal explants directly inhibited Shh expression. Tissue-specific Cre/loxP Foxf1/Foxf2 conditional knockouts in neural crest cells, RNA-seq, whole mount in situ hybridization, palatal explant culture with exogenous FGF18 protein PLoS genetics High 26745863
2016 FGF9 and FGF18 redundantly regulate all stages of skeletogenesis; compound loss of Fgf9 and Fgf18 alleles reveals variable potency along the proximodistal limb axis and affects expression of IHH, PTHrP, and RUNX2, placing FGF9/18 signaling upstream of these skeletal regulators. Combined Fgf9/Fgf18 null allele series, skeletal analysis, gene expression analysis Developmental biology High 26794256
2016 FGF9 and FGF18 promote survival and migration of human lung fibroblasts and inhibit TGFβ1-induced myofibroblast differentiation partially through FGFR3 (siRNA knockdown of FGFR3 impaired p-ERK activation by FGF9 and FGF18 and their effects on differentiation and migration). Primary human lung fibroblast cultures, siRNA knockdown of FGFR isoforms, ERK phosphorylation assay, apoptosis assay, migration assay, differentiation markers American journal of physiology. Lung cellular and molecular physiology Medium 26773067
2017 FGF18 activates the AKT/GSK3β/β-catenin signaling pathway in breast cancer cells, promoting EMT and cell migration. FGF18 increased Akt-Ser473 and Thr308 phosphorylation and GSK3β-Ser9 phosphorylation; β-catenin bound to target gene promoters was confirmed by ChIP. Western blotting (phosphorylation assays), wound-healing migration assay, chromatin immunoprecipitation (ChIP), clonogenicity assay Cellular physiology and biochemistry Medium 30196303
2017 FGF18 promotes angiogenesis in hepatocellular carcinoma by enhancing Wnt/β-catenin-mediated FGF18 expression via RPS15A; FGF18 binds FGFR3 on endothelial cells to activate AKT and ERK pathways. HCC cell line co-culture with endothelial cells, RPS15A overexpression/knockdown, in vivo xenograft, western blotting (AKT/ERK phosphorylation) Oncogene Medium 29242604
2018 FGF18 is required for acetylcholine receptor (AChR) clustering and neuromuscular junction (NMJ) formation. FGF18 is expressed in spinal motor neurons and localized at NMJs. Fgf18−/− embryos show reduced NMJ size, simplified motor endplates, reduced Chrne and Colq expression, and low-amplitude miniature endplate potentials. In C2C12 myotubes, FGF18 enhanced AChR clustering via FGFR and MEK1 signaling. Fgf18−/− knockout mice, laser capture microdissection, immunofluorescence localization, electrophysiology (mEPP recording), C2C12 cell AChR clustering assay with FGFR/MEK1 inhibitors Scientific reports High 29323161
2020 FGF18-FGFR2 signaling activates the c-Jun–YAP1 axis in gastric cancer: stimulation of FGFR2 with recombinant FGF18 induces F-actin formation, nuclear accumulation of YAP1, and overexpression of YAP1 targets, effects attenuated by FGFR2 depletion or AZD4547. FGF18-FGFR2 upregulates YAP1 through c-Jun, an effector of MAPK signaling. Recombinant FGF18 stimulation, FGFR2 siRNA knockdown, AZD4547 pharmacological inhibition, RNA-seq, immunofluorescence of YAP1 nuclear translocation Oncogene Medium 32934314
2020 Sprifermin (rhFGF18) is transiently internalized in chondrocytes through clathrin- and dynamin-independent endocytosis, is intracellularly degraded together with FGFR3, causing receptor desensitization. Receptor activation is not required for sprifermin endocytosis. Removal of sprifermin allows re-sensitization of cells. Western blot, cell staining for endocytic pathway markers, ERK1/2 activation assay, pharmacological inhibition of clathrin/dynamin pathways Experimental cell research Medium 32798495
2022 TGF-β signaling in neural crest-derived perimysial fibroblasts, cooperating with transcription factor Creb5, activates Fgf18 expression to support pharyngeal muscle development. Exogenous FGF18 partially rescues myogenic cell numbers in Osr2 mutants lacking TGF-β signaling. Conditional Osr2-Cre TGF-β signaling knockouts, single-cell RNAseq, in vivo exogenous FGF18 rescue, in situ hybridization eLife High 36542062
2022 HDAC7 promotes FGF18 expression via reducing β-catenin acetylation at Lys49 and phosphorylation at Ser45, facilitating nuclear translocation of β-catenin which then activates FGF18 transcription through TCF4 binding. USP10 deubiquitinase interacts with and stabilizes HDAC7. Co-immunoprecipitation, western blotting for post-translational modifications, lentiviral overexpression/knockdown in vivo and in vitro, gene rescue experiments Journal of experimental & clinical cancer research Medium 35277183
2023 FGF18 secreted by hepatic stellate cells alleviates hepatic ischemia-reperfusion injury through the USP16/KEAP1/Nrf2 pathway: FGF18 reduces USP16 levels, leading to increased ubiquitination of KEAP1 and activation of Nrf2. USP16 interacts with and deubiquitinates KEAP1, and Nrf2 directly binds the USP16 promoter, forming a negative feedback loop. HSC-specific FGF18 deletion, Co-IP (USP16-KEAP1), ubiquitination assays, ChIP (Nrf2 binding to USP16 promoter), western blotting Nature communications High 37777507
2023 FGF18 promotes human lung branching morphogenesis by regulating mesenchymal progenitor cells: FGF18 treatment of human fetal lung explants promotes branching, increases epithelial proliferation, maintains SOX2/SOX9 double-positive distal bud progenitors, and increases expression of SOX9, FN1, and COL2A1 in mesenchyme. Human fetal lung explant culture (air-liquid interface), recombinant FGF18 protein treatment, immunofluorescence, gene expression analysis American journal of physiology. Lung cellular and molecular physiology Medium 36791060
2024 BUB1 promotes FGF18 expression by interacting with METTL3 to induce m6A methylation of TRAF6 mRNA, thereby activating the NF-κB/FGF18 transcriptional axis in gastric cancer cells. Co-immunoprecipitation (BUB1-METTL3), MeRIP-qPCR (m6A of TRAF6), RNA-seq, western blotting, siRNA/overexpression in vivo and in vitro Life sciences Medium 39025206
2025 FGF18 facilitates intercellular communication between hepatic stellate cells and myofibroblasts in liver fibrosis by efficiently inducing osteopontin (Spp1/OPN) expression in culture-activated αSMA+ HSCs (but not in quiescent HSCs); OPN in turn upregulates profibrotic genes in quiescent HSCs. FGF18 and TGFβ synergistically increase OPN expression. Myofibroblast-derived Spp1 signals back to HSCs, forming a feedforward fibrotic loop. In vitro HSC/myofibroblast cultures (activated vs. quiescent), FGF18 and TGFβ stimulation, immunohistochemistry, cell-cell communication analysis of murine liver fibrosis models iScience Medium 40678531
2014 FGF18 expressed in the distal limb mesenchyme induces premature expression of myogenic determination genes Myf5 and MyoD in chick limb myoblasts via ERK MAP kinase signaling (not PI3K). Retinoic acid inhibits the myogenic activity of FGF18, and blocking RA signaling allows premature FGF18-induced MyoD expression. Chick limb bud explant/electroporation assays, pharmacological inhibition of ERK/PI3K, retinoic acid addition/inhibition, in situ hybridization for myogenic genes Developmental biology Medium 25446536

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis. Genes & development 371 11937494
2005 Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis. The Journal of biological chemistry 204 15781473
1998 Comparison of the expression of three highly related genes, Fgf8, Fgf17 and Fgf18, in the mouse embryo. Mechanisms of development 169 9651520
2006 FGF18 is required for early chondrocyte proliferation, hypertrophy and vascular invasion of the growth plate. Developmental biology 147 17014841
2003 Involvement of the FGF18 gene in colorectal carcinogenesis, as a novel downstream target of the beta-catenin/T-cell factor complex. Cancer research 144 14559787
1998 Structure and expression of the mRNA encoding a novel fibroblast growth factor, FGF-18. The Journal of biological chemistry 137 9660775
2001 Regulation of osteoblast, chondrocyte, and osteoclast functions by fibroblast growth factor (FGF)-18 in comparison with FGF-2 and FGF-10. The Journal of biological chemistry 128 11741978
1998 FGF-18, a novel member of the fibroblast growth factor family, stimulates hepatic and intestinal proliferation. Molecular and cellular biology 123 9742123
2024 Injectable Microgels with Hybrid Exosomes of Chondrocyte-Targeted FGF18 Gene-Editing and Self-Renewable Lubrication for Osteoarthritis Therapy. Advanced materials (Deerfield Beach, Fla.) 117 38266145
2005 Comprehensive analysis of FGF and FGFR expression in skin: FGF18 is highly expressed in hair follicles and capable of inducing anagen from telogen stage hair follicles. The Journal of investigative dermatology 115 15854025
2003 FGF17b and FGF18 have different midbrain regulatory properties from FGF8b or activated FGF receptors. Development (Cambridge, England) 105 14602678
2012 Cholesteryl group- and acryloyl group-bearing pullulan nanogel to deliver BMP2 and FGF18 for bone tissue engineering. Biomaterials 101 22800537
2012 Hair cycle resting phase is regulated by cyclic epithelial FGF18 signaling. The Journal of investigative dermatology 100 22297635
2016 FGF9 and FGF18 in idiopathic pulmonary fibrosis promote survival and migration and inhibit myofibroblast differentiation of human lung fibroblasts in vitro. American journal of physiology. Lung cellular and molecular physiology 94 26773067
2006 Direct interactions of Runx2 and canonical Wnt signaling induce FGF18. The Journal of biological chemistry 84 17158875
2016 A Shh-Foxf-Fgf18-Shh Molecular Circuit Regulating Palate Development. PLoS genetics 78 26745863
2013 Foxp1 maintains hair follicle stem cell quiescence through regulation of Fgf18. Development (Cambridge, England) 73 23946441
2000 Involvement of fibroblast growth factor (FGF)18-FGF8 signaling in specification of left-right asymmetry and brain and limb development of the chick embryo. Mechanisms of development 72 10906450
2004 Fgf18 is required for embryonic lung alveolar development. Biochemical and biophysical research communications 68 15336546
2001 Two animal models of retinal degeneration are rescued by recombinant adeno-associated virus-mediated production of FGF-5 and FGF-18. Molecular therapy : the journal of the American Society of Gene Therapy 67 11319911
2007 FGF18 in colorectal tumour cells: autocrine and paracrine effects. Carcinogenesis 66 17890768
2020 Circular RNA circPDE4D Protects against Osteoarthritis by Binding to miR-103a-3p and Regulating FGF18. Molecular therapy : the journal of the American Society of Gene Therapy 65 33125858
2004 FGF18 represses noggin expression and is induced by calcineurin. The Journal of biological chemistry 64 15252029
2017 Ribosomal protein S15a promotes tumor angiogenesis via enhancing Wnt/β-catenin-induced FGF18 expression in hepatocellular carcinoma. Oncogene 62 29242604
2023 FGF18 alleviates hepatic ischemia-reperfusion injury via the USP16-mediated KEAP1/Nrf2 signaling pathway in male mice. Nature communications 58 37777507
2022 HDAC7 promotes NSCLC proliferation and metastasis via stabilization by deubiquitinase USP10 and activation of β-catenin-FGF18 pathway. Journal of experimental & clinical cancer research : CR 58 35277183
2007 A review of FGF18: Its expression, signaling pathways and possible functions during embryogenesis and post-natal development. Histology and histopathology 54 17128416
2016 A combined series of Fgf9 and Fgf18 mutant alleles identifies unique and redundant roles in skeletal development. Developmental biology 51 26794256
2020 Enhanced chondrogenic phenotype of primary bovine articular chondrocytes in Fibrin-Hyaluronan hydrogel by multi-axial mechanical loading and FGF18. Acta biomaterialia 47 31982592
2018 FGF18, a prominent player in FGF signaling, promotes gastric tumorigenesis through autocrine manner and is negatively regulated by miR-590-5p. Oncogene 46 30082912
2017 Injectable Shear-Thinning CaSO4/FGF-18-Incorporated Chitin-PLGA Hydrogel Enhances Bone Regeneration in Mice Cranial Bone Defect Model. ACS applied materials & interfaces 46 29143524
2004 FGF-18 is upregulated in the postnatal rat lung and enhances elastogenesis in myofibroblasts. American journal of physiology. Lung cellular and molecular physiology 46 15447937
2015 Deletion of the PH-domain and Leucine-rich Repeat Protein Phosphatase 1 (Phlpp1) Increases Fibroblast Growth Factor (Fgf) 18 Expression and Promotes Chondrocyte Proliferation. The Journal of biological chemistry 45 25953896
2018 FGF18 Enhances Migration and the Epithelial-Mesenchymal Transition in Breast Cancer by Regulating Akt/GSK3β/Β-Catenin Signaling. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 43 30196303
2013 Divergence of intracellular signaling pathways and early response genes of two closely related fibroblast growth factors, FGF8 and FGF18, in bovine ovarian granulosa cells. Molecular and cellular endocrinology 40 23707615
2021 Combinatorial effect of nano whitlockite/nano bioglass with FGF-18 in an injectable hydrogel for craniofacial bone regeneration. Biomaterials science 39 33464240
2020 Identification of a FGF18-expressing alveolar myofibroblast that is developmentally cleared during alveologenesis. Development (Cambridge, England) 39 31862844
2007 The core protein of growth plate perlecan binds FGF-18 and alters its mitogenic effect on chondrocytes. Archives of biochemistry and biophysics 39 17971291
2011 Fgf-18 is required for osteogenesis but not angiogenesis during long bone repair. Tissue engineering. Part A 38 21457097
2020 FGF18-FGFR2 signaling triggers the activation of c-Jun-YAP1 axis to promote carcinogenesis in a subgroup of gastric cancer patients and indicates translational potential. Oncogene 36 32934314
2011 Profiling target genes of FGF18 in the postnatal mouse lung: possible relevance for alveolar development. Physiological genomics 35 21878612
2002 FGF-18 is a neuron-derived glial cell growth factor expressed in the rat brain during early postnatal development. Brain research. Molecular brain research 35 12399108
2010 Retinoic acid controls expression of tissue remodeling genes Hmgn1 and Fgf18 at the digit-interdigit junction. Developmental dynamics : an official publication of the American Association of Anatomists 32 20034106
2007 Krüppel-like zinc finger protein Glis3 promotes osteoblast differentiation by regulating FGF18 expression. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 32 17488195
2012 Investigating the role of FGF18 in the cultivation and osteogenic differentiation of mesenchymal stem cells. PloS one 31 22937141
2021 Suppression of FGF5 and FGF18 Expression by Cholesterol-Modified siRNAs Promotes Hair Growth in Mice. Frontiers in pharmacology 30 34305588
2016 Use of FGF-2 and FGF-18 to direct bone marrow stromal stem cells to chondrogenic and osteogenic lineages. Future science OA 29 28116125
2016 Osteopromoting Reservoir of Stem Cells: Bioactive Mesoporous Nanocarrier/Collagen Gel through Slow-Releasing FGF18 and the Activated BMP Signaling. ACS applied materials & interfaces 28 27649064
2013 FGF18 accelerates osteoblast differentiation by upregulating Bmp2 expression. Congenital anomalies 25 23751042
2019 Generation and validation of novel conditional flox and inducible Cre alleles targeting fibroblast growth factor 18 (Fgf18). Developmental dynamics : an official publication of the American Association of Anatomists 24 31290205
2025 Delivery of FGF18 using mRNA-LNP protects the cartilage against degeneration via alleviating chondrocyte senescence. Journal of nanobiotechnology 23 39844298
2017 Decrease of miR-195 Promotes Chondrocytes Proliferation and Maintenance of Chondrogenic Phenotype via Targeting FGF-18 Pathway. International journal of molecular sciences 23 28471382
2023 Role of FGF-18 in Bone Regeneration. Journal of functional biomaterials 22 36662083
2010 A novel regulatory mechanism for Fgf18 signaling involving cysteine-rich FGF receptor (Cfr) and delta-like protein (Dlk). Development (Cambridge, England) 22 20023171
2022 Regulation of FGF-2, FGF-18 and Transcription Factor Activity by Perlecan in the Maturational Development of Transitional Rudiment and Growth Plate Cartilages and in the Maintenance of Permanent Cartilage Homeostasis. International journal of molecular sciences 20 35216048
2024 Targeted Therapy of Osteoarthritis via Intra-Articular Delivery of Lipid-Nanoparticle-Encapsulated Recombinant Human FGF18 mRNA. Advanced healthcare materials 19 39363784
2014 Interactions between FGF18 and retinoic acid regulate differentiation of chick embryo limb myoblasts. Developmental biology 19 25446536
2019 Expression of FGF8, FGF18, and FGFR4 in Gastroesophageal Adenocarcinomas. Cells 18 31527546
2018 Synergistic Effects of FGF-18 and TGF-β3 on the Chondrogenesis of Human Adipose-Derived Mesenchymal Stem Cells in the Pellet Culture. Stem cells international 18 29861742
2005 Comparative genomics on FGF8, FGF17, and FGF18 orthologs. International journal of molecular medicine 18 16077960
2024 BUB1 potentiates gastric cancer proliferation and metastasis by activating TRAF6/NF-κB/FGF18 through m6A modification. Life sciences 17 39025206
2017 FGF18 inhibits MC3T3‑E1 cell osteogenic differentiation via the ERK signaling pathway. Molecular medicine reports 17 28765932
2021 miR-590-5p affects chondrocyte proliferation, apoptosis, and inflammation by targeting FGF18 in osteoarthritis. American journal of translational research 15 34539990
2020 FGF18 Inhibits Clear Cell Renal Cell Carcinoma Proliferation and Invasion via Regulating Epithelial-Mesenchymal Transition. Frontiers in oncology 15 33117668
2016 Endometrial Cancer-Associated FGF18 Expression Is Reduced by Bazedoxifene in Human Endometrial Stromal Cells In Vitro and in Murine Endometrium. Endocrinology 15 27267714
2012 FGF18 augments osseointegration of intra-medullary implants in osteopenic FGFR3(-/-) mice. European cells & materials 15 22828989
2024 FGF18 alleviates sepsis-induced acute lung injury by inhibiting the NF-κB pathway. Respiratory research 14 38419044
2022 TGF-β signaling and Creb5 cooperatively regulate Fgf18 to control pharyngeal muscle development. eLife 14 36542062
2019 Recombinant human FGF18 preserves depth-dependent mechanical inhomogeneity in articular cartilage. European cells & materials 14 31393594
2023 FGF-18 alleviates memory impairments and neuropathological changes in a rat model of Alzheimer's disease. Neuropeptides 13 37506425
2020 Sprifermin (recombinant human FGF18) is internalized through clathrin- and dynamin-independent pathways and degraded in primary chondrocytes. Experimental cell research 12 32798495
2017 FGF18 protects against 6-hydroxydopamine-induced nigrostriatal damage in a rat model of Parkinson's disease. Neuroscience 12 28504195
2024 FGF18 encoding circular mRNA-LNP based on glycerolipid engineering of mesenchymal stem cells for efficient amelioration of osteoarthritis. Biomaterials science 11 39037353
2023 FGF18 promotes human lung branching morphogenesis through regulating mesenchymal progenitor cells. American journal of physiology. Lung cellular and molecular physiology 11 36791060
2022 Ginsenoside Rb1 from Panax ginseng attenuates monoiodoacetate-induced osteoarthritis by inhibiting miR-21-5p/FGF18-mediated inflammation. Journal of food biochemistry 11 35866931
2018 Lack of Fgf18 causes abnormal clustering of motor nerve terminals at the neuromuscular junction with reduced acetylcholine receptor clusters. Scientific reports 11 29323161
2020 Evaluation of Relationship Between Common Variants in FGF18 Gene and Knee Osteoarthritis Susceptibility. Archives of medical research 10 32109713
2020 Tissue-specific analysis of Fgf18 gene function in palate development. Developmental dynamics : an official publication of the American Association of Anatomists 9 33034111
2023 Sympathetic Neurotransmitter, VIP, Delays Intervertebral Disc Degeneration via FGF18/FGFR2-Mediated Activation of Akt Signaling Pathway. Advanced biology 8 38047500
2015 FGF18 as a potential biomarker in serous and mucinous ovarian tumors. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 8 26427667
2020 Estrogen-Induced Stromal FGF18 Promotes Proliferation and Invasion of Endometrial Carcinoma Cells Through ERK and Akt Signaling. Cancer management and research 7 32801905
2016 FGF18 signaling in the hair cycle resting phase determines radioresistance of hair follicles by arresting hair cycling. Advances in radiation oncology 7 28740887
2023 FGF-18 Protects the Injured Spinal cord in mice by Suppressing Pyroptosis and Promoting Autophagy via the AKT-mTOR-TRPML1 axis. Molecular neurobiology 6 37581847
2022 Preclinical Use of FGF-18 Augmentation for Improving Cartilage Healing Following Surgical Repair: A Systematic Review. Cartilage 6 36541606
2024 Single Injection AAV2-FGF18 Gene Therapy Reduces Cartilage Loss and Subchondral Bone Damage in a Mechanically Induced Model of Osteoarthritis. Current gene therapy 5 38783531
2024 HIF-1α induced FGF18 alleviates renal ischemia/reperfusion injury via YAP. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 5 39373977
2023 FGF18. Differentiation; research in biological diversity 5 38007374
2025 Enhanced yield and subtype identity of hPSC-derived midbrain dopamine neuron by modulation of WNT and FGF18 signaling. bioRxiv : the preprint server for biology 4 39829874
2024 Overexpression of Fgf18 in cranial neural crest cells recapitulates Pierre Robin sequence in mice. Frontiers in cell and developmental biology 4 38694818
2023 Preferential FGF18/FGFR activity in pseudoglandular versus canalicular stage human lung fibroblasts. Frontiers in cell and developmental biology 4 37701781
2025 Intercellular communication between hepatic stellate cells and myofibroblasts mediated by osteopontin and FGF18 promotes liver fibrosis. iScience 3 40678531
2023 A high-sensitivity ELISA for detection of human FGF18 in culture supernatants from tumor cell lines. Biochemical and biophysical research communications 3 37453260
2023 Computer-assisted stabilization of fibroblast growth factor FGF-18. Computational and structural biotechnology journal 3 37920818
2021 FGF18 modulates CTGF mRNA expression in cumulus-oocyte complexes and early bovine embryos: preliminary data. Zygote (Cambridge, England) 3 34405788
2025 Transcriptome integration analysis revealed that miR-103-3p regulates goat myoblast proliferation by targeting FGF18. BMC genomics 2 39773020
2025 FGF18 induces chondrogenesis and anti-osteoarthritic effects in a mouse model for TMJ degeneration. PloS one 2 40273050
2023 MiR-21 regulated hair follicle cycle development in Cashmere goats by targeting FGF18 and SMAD7. Animal biotechnology 2 36897050
2009 Correlation of the SNPs of FGFR1, FGF10, FGF18 with nonsyndromic cleft lip with or without palate in Chinese population. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 2 19727229
2018 Association study of FGF18 with developmental dyslexia in Chinese population. Psychiatric genetics 1 29240020
2024 FGF18 impairs blastocyst viability, DNA double-strand breaks and maternal recognition of pregnancy genes. Theriogenology 0 38796960

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